Characterization of Two New Potential Impurities of Valsartan Obtained Under Photodegradation Stress Condition

ROMINA M. BIANCHINI; PATRICIA M. CASTELLANO; TEODORO S. KAUFMAN

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2011

0731-7085

photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV–vis radiation( > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparativeamounts of the new potential degradation products (DP-1 and DP-2) were obtained bysubmitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparativenormal phase column chromatography. Analytical information from the infrared, nuclearmagnetic resonance and mass spectral data of the degradation products revealed their structuresas N-[2-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3-f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL,while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitantcyclization to yield a tetracyclic diazacyclopropene derivative